As the population has grown older due to improvement in health conditions, one of the attendant consequences is that stomach problems which plague many older people are more prevalent. Normally, the problem is simple heartburn caused by excess stomach acid and gas. The same effect often occurs from the frenetic pace of modern life. The over-the-counter or OTC market is filled with antacid preparations to ameliorate this problem. These preparations normally include bases in the form of metal hydroxides, metal carbonates and bicarbonates and metal hydrosilicates which act as buffering agents for the excess stomach acid. Commonly used metals are aluminum, calcium, magnesium and in some instances sodium. However, the multivalent ions are more commonly used because too much sodium can be dangerous for those with some form of heart condition.
The metal bases are normally in the form of relatively large particles or particulates which form a colloid or suspension in an aqueous carrier. The antacid may also include other additives such as an antiflatulence agent to minimize gas buildup as well as some form of flavoring to make the mixture more palatable.
While the antacid preparations available in the OTC market are fairly effective at the requisite buffering action, many people must take these antacid preparations several times a day because the duration of effectiveness is fairly short. In fact, although the manufacturers will normally recommend that these preparations will be taken no more than four times a day because of metal ion toxicity, the actual duration of effectiveness of each dose in the gastric and upper intestinal system is in the order of forty-five minutes to an hour, after which the antacids are cleared. In order to counteract this clearing problem, several manufacturers have gone to the so-called "extra-strength" products which merely double the amount of base in the antacid product. The theory behind these extra strength products is that even as most of the base is cleared from the effective zone, the residual amount will have sufficient buffering strength to at least partially ameliorate the acid build-up problem. However, no one has previously developed a way of keeping a significant amount of base in the active gastric and upper intestinal systems for a longer duration.
The present invention solves this extended duration problem with the use of lipid vesicles as an integral part of the antacid product. While lipid vesicles, particularly the phospholipid vesicles called liposomes, have been discussed for use in a variety of pharmaceutical, cosmetic and personal care products, they are normally not considered for enteral use because liposomes, being made of phospholipids, are readily hydrolysed by both phospholipases and acid lipases. The gastrointestinal intestinal tract is replete with these lipases and phospholipid vesicles break down much too quickly to be of any real use. Although there are acid stabilized phospholipids which have been made into vesicles (see U.S. Pat. No. 4,221,732), these have not been used for a commercial OTC enteral product for cost reasons. Phospholipids which are sufficiently pure for an enteral product are expensive, costing hundreds of dollars per kilogram, and the acid stabilized phospholipids are even more expensive. Accordingly, although it may be feasible to make enteral products having vesicles which are acid stable so that they can be used in the gastrointestinal tract, it is not economically practical.
However, changes in lipid vesicle technology in the last few years are now making it possible to use lipid vesicles in OTC products. The reason is that a variety of new materials have been successfully tried as vesicle formers in place of phospholipids. U.S. Pat. Nos. 4,911,928, 5,147,723, and 5,032,457 and well as U.S. patent application Ser. No. 761,253, the disclosures of which are incorporated herein by reference, all show much less expensive materials which can be made successfully into vesicles. In addition, vesicle making procedures are also being modified to use faster, more cost efficient methods. U.S. Pat. Nos. 4,895,452 and 5,013,497, the disclosures of which are also incorporated herein by reference, describe apparatus and methods for rapid vesicle formation whereby the lipid vesicles are formed in milliseconds with throughparts in the ? liter/hour range. The ability to form vesicles in this high volume mode, coupled with the use of less expensive materials, has finally brought the price of lipid vesicles into the region it is economically feasible for OTC enteral products. In addition, since these new materials are not phospholipids they are not subject to degradation by phospholipases. Selected materials are also not subject to the acid lipases. As such, they can provide the vesicles which have long term stability in the gastrointestinal tract.
Accordingly, it is an object of the invention to provide an antacid product having extended duration in the gastric and upper intestinal systems.
Another object of the invention is to provide an antacid product which includes lipid vesicles.
A further object of the invention is to provide a method of extending the duration or residence time of actives from an antacid in the gastric and upper intestinal tract.
These and other objects and features of the invention will be apparent from the following description.